This competitive revision is to enlarge the scope of the current R01 - 'Dysfunctional Corticolimbic Activity and Connectivity in Bipolar Disorder'to also study at baseline 20 bipolar disorder (BD) patients in the euthymic state (BDE) and 40 unaffected siblings (UAS) of BD patients, and is in response to Notice Number (NOT-OD- 09-058), titled: "NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications". The parent grant proposes to concurrently measure both corticoamygdalar connectivity as well as regional limbic activation in 40 unmedicated BD patients in manic phase (BDM) and 40 in the depressed phase (BDD) before and after treatment with lithium as well as 40 matched healthy control subjects. The a priori defined regions of interest are the cortical mood regulating region - ventral anterior cingulate cortex (vACC) and the amygdala. The first aim is to measure corticoamygdalar connectivity using a novel connectivity specific measure - resting state low frequency BOLD fluctuations (LFBF) correlations. The second aim is to measure amygdalar activation using an active facial emotion recognition task. Preliminary data analysis has revealed interesting results which suggest that amygdalar activation is increased and corticoamygdalar connectivity is decreased in BD compared to healthy subjects and this abnormality is state independent being present in both BDD and BDM patients. Furthermore, BD patients with a family history of mood disorder in a first degree relative have a greater decrease in corticoamygdalar connectivity than the ones without a family history. These findings suggest that corticoamygdalar connectivity and amygdalar activation in response to face task could be used as endophenotypes to investigate the genetic etiology of BD. However, to further strengthen these findings we also need to study BDE patients and UAS of BD patients. While conducting the parent study, we have screened a number of such subjects who we cannot study at this time as funding is not available. Therefore, this competing revision is being applied for to ask for a modest amount of supplement to investigate baseline corticoamygdalar activation and connectivity abnormalities in BDE and UAS of BD patients. Inclusion of these two groups will complement the overall aim of the parent study - investigating the circuit level corticoamygdalar abnormalities which may be inherent to the genetic and neurobiological etiology of BD. PUBLIC HEALTH RELEVANCE: This competing revision of the parent grant - 'Dysfunctional Corticolimbic Activity and Connectivity in Bipolar Disorder and Effect of Lithium'which is studying 40 manic, 40 bipolar depressed and 40 healthy subjects is being submitted to enlarge the scope of the parent grant to also study 20 euthymic bipolar patients and 40 unaffected siblings of bipolar patients. This study will complement the parent grant aims to elucidate the genetic and neurobiological etiology of bipolar disorder.